Our observation that rats kept on a diet deficient in choline and methionine (CMD) develop hepatocellular carcinoma (23/45) within 13 to 24 months while the control group on the same diet but with added choline chloride (0.8%) develop no neoplastic or preneoplastic lesions has prompted us to explore this phenomena in greater depth. We also found that nuclear lipid peroxidation and DNA damage occurs very early in the liver of rat ingesting CMD diet. That dietary deficiency alone without any added carcinogen might cause cancer has a profound significance not only from the mechanistic but also from human point of view, since methionine is one of the amino acids present in relatively low amounts in many plant proteins. The objectives of this proposal are (i) to study the possible role of methionine in CMD induced liver carcinogenesis and (ii) to probe into the mechanism by which CMD diet produces hepatocellular carcinoma. The role of lipid peroxidation and DNA damage, biochemical alterations induced by feeding CMD diet, in the carcinogenic process will be explored in respect to initiation, promotion and progression.